© 1995 American Heart Association, Inc.
Articles |
Immune Complexes of LDL Induce Atherogenic Responses in Human Monocytic Cells
From the Department of Autoimmunity and Transplantation, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Wash (P.A.K., B.M.R., P.M.D., S.A.Y., R.I.G.), and the Department of Microbiology, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Conn (G.A.W.).
Correspondence to Peter A. Kiener, Bristol-Myers Squibb Pharmaceutical Research Institute, 3005 First Ave, Seattle, WA 98121.
Abstract The ability of immune complexes of LDL or acetylated LDL (acLDL), together with antibodies to LDL, to induce a proatherogenic phenotype in human monocytic cells has been explored. Treatment of THP-1 monocytic cells or peripheral human monocytes with LDL immune complexes containing intact anti-LDL markedly enhanced the ability of these cells to subsequently bind and take up LDL, whereas aggregated LDL or LDL immune complexes prepared with F(ab')2 fragments of anti-LDL had no significant effect. Activation of THP-1 cells with intact LDL immune complexes also stimulated mRNA expression for the scavenger receptor. Additionally, activation of THP-1 cells with insoluble immune complexes of LDL or LDL stimulated generation of reactive oxygen intermediates that, in turn, could oxidize exogenous LDL. These results indicate that the binding of lipoprotein immune complexes to Fc receptors on monocytic cells activates a series of responses that could accelerate the initiation or progression of atherosclerosis.
Key Words: lipoproteins • scavenger receptors • Fc receptor • anti-LDL • TNF-
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